Acid-base indicator dyestuffs



ulw smd United States i atent" ACID-BASE INDICATOR'DYESTUFFS Gerold Schwarzenbach, Zurich, and Richard Sallmann, Basel, Switzerland, assignors to CibaLimited, Basel, Switzerland, a Swiss firm No Drawing. Application August 25, 1952, Serial'No; 306,284

Claims priority, application Switzerland-August 29, 1951 12 Claims. (Chili-230) CHz-C O OH CHa-..N

CHz-C O OH be reacted with formaldehyde or'a compound yielding formaldehyde'and with an iminodiacetic acid or a salt or'functional derivative of such acid. The condensation is advantageously conducted in the presence of an aqueous solution of an" alkali hydroxide, if desired, with the'addinonof a water-solubleorganic solvent, such as methyl alcohol, ethyl alcohol, acetone or dioxane. The. reactionis carried out atroom temperature or a raised temperature, for example, 50-70 C. The formaldehyde may be used'in the form: of para-formaldehyde, advantageously it is. used in the form of a.concentrated aqueous solution. When, instead of the free iminodiacetic acid, a functional'derivative thereof is used for the condensation such as the nitrile or an ester, the

reaction is followed by a hydrolysis to produce the free acid.

Instead of causingthe three components to react together at the same time, a methylol-compound may first be formed from the indicator dyestuif and formaldehyde, and the methylolcompoundcan then be. condensed with the imino diacetic acid in aqueous alkaline solution. Alternatively, the methylol compound. may be. reacted with a derivative, for example, an. ester, of the imino-. diacetic acidin the.'presence;.of; an' acid, for example, acetic acid, and then the resulting ester is saponified.

Finally, the indicator dyestutfmay first be converted into a halogen-methyl compound, for example, a chloromethyl compound. Thereaction .of the resultinghalogenmethyl compound .with the iminodiacetic acid or a salt or functional derivative thereof, is thenadvantageously carried out by heatingthe. components, advantageously with the addition of an organic solvent, such as benzene, toluene, xylene, low boiling benzine, ethyl acetate, alcohol, butanol, etc. Itisofadvantage to use two molecular proportions ofthe iminodiacetic acid forv each halogen; methyl group,- one molecular proportion-serving to: bind the-hydrohalic acidsformedwhich can be introduced into the indicator dyestulf in accordance with the present processdepends fir'stly on the constitution of the dyestufi, that is to say, onthe number of hydroxyl groups of phenolic character which it contains and of the:free positions vicinal thereto, and secondly on the relative proportionsin which the reaction components are used.

The derivatives of the-invention, which are derived from indicator dyestuffs: containing a hydroxyl group as an auxochromic group, containv at least once the: following atomic grouping on o om-o 0 on 2 x-t u 3CGHz--N our-coon in which X represents hydrogen or any desired organic radical or the grouping CH2-COOH 0112-00011 and in which the carbon atoms marked 1, 2 and 3 belong to an aromatic ring system, advantageously a 6-membered ring;

The indicator dyestuffs which are-converted'intoderivativesin accordance with the presentinvention, may belong to a very wide. variety of classes of compounds;

There may be mentioned'indicator azo-dyestufis such, for example, as 2:4-d.ihydroxy-4'-nitro-1:l'-azobenzene, 2:4 dihydroxy 1:1 azobenzene 4 sulfonic acid, 4 hydroxy 3' or 4" nitro 1: 1' azoben zene 3' carboxylic acid or salts thereof. Furthermore there may be mentioned nitro phenols, such as ortho-, metaor para-nitrophenol, 2:4'- or 2:5-dinitrophenol or 4-'nitro-- ortho-cresol. Especially valuable are dyestufis of the triph'enylmethanee series such as. phthaleins and suifophthaleins. As examples there may be mentioneddichlorophenol-sulfophthalein, dibromophenol-sulfophthalein, ortho-cresol-sulphophthalein, thymol-sulfophthalein, orthoor meta-cresol. phthalein, thymol-phthalein andespecially phenolphthalein.

Instead of introducing the radical into the finished indicator dyestufl? it is also possible to introduce the aforesaid radical into anintermediatemprodnot used for making the dyestuff and thereafter com.- pleting the synthesis of the dyestufi.

The new derivatives of'indicator dyestuifs obtainable in accordance with the invention are distinguished. by the fact that they form complex compounds with various metal ions. This formation of complexes may. be asso ciated with'a changein the color of the indicator dye-'- stuif. The derivatives of the indicator dyestufts, in which the formation of complexes with metal ions is associated with a change in color of the indicator, can be used for the analytical determination of'the metal ions in question. In other words, there is obtained from the acidbase indicator, which is sensitive to hydrogen ions, an indicator which is responsive to metal ions.

The indicator derivatives sensitive to metal ions canbe used mainly in two analytical methods, namely, in colorimetric and titrirnetric. analysis. in colorimetric analysis thestrength ofzthe. color. produced by complex for example a derivative of phenolphthalein which con= tains between 2 and 4 radicals CHZC OH CH2N c1120 0 OH is added to the solution to be tested. The indicator is thereby turned red. The solution is then titrated with an agent capable of forming complexes strongly with calcium ions, for example, nitrilo-triacetic acid or ethylene diamine-tetracetic acid until the indicator has assumed its original color. By means of the aforesaid indicator sulfate ions can also be determined by precipitating the sulfate ions with an excess of barium ions and subsequently back titrating the excessrof barium ions with a strong complex-forming agent. 7

The following examples illustrate the invention, the parts being by weight unless otherwise stated, and the relationship of parts by weight to parts by volume being the same as that of the kilogram to the liter:

Example 1 V 32.0 parts (1 mol) of phenolphthalein are dissolved in a mixture of 100 parts of water and 30 parts by volume of caustic'soda solution of 30 per cent. strength. There are then added while stirring 53.2 parts (4 mols) of irninodiacetic acid dissolved in a mixture of 80 parts of water and 68 parts by volume of caustic soda solution of 30 per cent. strength. 41 parts of an aqueous solution of'fo'rmaldehyde 'of 37 per cent. strength are then added dropwise, and the reaction mixture is then heated for 8 hours at 6070 C. After cooling the mixture and diluting it with water, it is acidified with dilute hydrochloric acid, the precipitated condensation product is separated by filtering with suction and recrystallized from alcohol.

Example.2

' 7.0 parts of ortho-cresolphthalein are dissolved in a mixture'of 20 parts by volume. of alcohol, pms 'of 7 water and 4 parts by volume of caustic soda solution of 30 per cent. strength. There is then added a solution of -5.8 parts of iminodiacetic acid in 8 parts of water and 7 parts by volume of caustic soda solution of 30 per cent. strength. 4.0 parts of an aqueous formaldehyde solution of 37 per cent. strength are then added dropwise while stirring, and, when the addition is complete the mixture is heated for 2 hours at 6070 C. At the end of this Example 3 A solution of 107 parts of iminodiacetic acid dimethyl ester in ethyl acetate is added dropwise, while stirring, to a solution of 62 parts of 4-nitro-2-chloromethylphenol in 300 parts by volume of ethyl acetate, while cooling with ice. After a short time crystals of the hydrochloride of iminodiacetic acid dimethyl ester begin to separate. After heating the reaction mixture for 2 hours at 4-050 C., the precipitated salt is filtered off, washed with ethyl There is obtained a pale pink powder, which.

4 acetate, and the filtrate is evaporated to dryness. The 3-nitro-6-hydioxybenzylamino-diacetic acid dimethyl' ester is obtained in theoretical yield in the form of yellow crystals. After recrystallization from alcohol it melts at 96.5-97.5 C.

In order to hydrolyze the ester, 9.3 parts thereof are dissolved in 40 parts of alcohol and a total of 18 parts by volume of caustic soda solution of 15 per cent. strength is added in portions to the solution at 4050 C. After 30 minutes the hydrolysis is finished. Then the reaction mixture is evaporated to dryness at 40-50 C. in vacuo, the residue is dissolved, and the acid is precipitated by acidification with dilute hydrochloric acid. There is obtained 3-nitro-6-hydroxybenzylaminodiacetic acid in the form of apale yellow powder.

Example 4 9.2 parts of the azo dyestufi from diazotized 4-chlorol-aminobenzene and hydroxybenzene are dissolved in a mixture of 20 parts by volume'of ethylalcohol and 4 parts by'volumeof sodium hYdl'OXldQ'SOllltlOH of 30 per cent strength. There is then added while stirring a solution of 6.8 parts of iminodiacetic acid, 10 parts of water and 7.4 parts by volume of sodium hydroxide Example 5 26.6 parts of iminodiacetic acid are dissolved in 20 parts of Water and 38 parts by volume of sodium hydroxide solution of 30 per cent strength. A solution of 30 parts of 4-acetylamino-l-hydroxybenzene, 20 parts of water and 20 parts by volume of sodium hydroxide solution of 30 percent strength is added, and then;l8 parts of a formaldehyde solution of 37 per cent strength are added while stirring. After stirring for 5 hours at 60-70 C., the. reaction mixture isacidified with hydrochloric acid and evaporated to dryness in vacuo. The residue is stirred in the warm with parts of hydrochloric acid of 20 per cent strength, whereby the product is dissolved, but the greater part of the resulting sodium chloride remains undissolved. After filtering ofi the residueand Washing it with hydrochloric acid, the filtrate is boiled under reflux for one hour and then evaporated to dryness in vacuo. The residue obtained in the form of ,a' pale yellow solid productis the dihydrochloride otthecom pound of the formula CHr-Q O OH GHa-N V This dihydrochloride is diazotized'in the usual mannerwith sodium nitrite and coupled in an alkaline medium, for example, with phenol or resorcinol 7 Example 6 Datum/[matron or BARIUM trodu'ced (15 20 drops of-"a solutionucontainingxt021 in -at=-least one-position 'vicinal to ana auxoohromictgroupr 81111312 ofitlle wildfillsEIfiOIF-PIQductifl'bll'l1 1 l -Pheselected. from theiclass consisting- 0f:unsubstitutedraminoc: nolphthalern, 4 mols of'formaldehyde and mols of' groups and hydroxyl groups f,phenolic,:eharacter the-.1 rmmodiacetic acid and 1.cc. of a molar solution of soamino and hydroxylrgmups b i b dz monocyclic;

dium acetate, per 100 cc. of solution), and titration is 5: carried out with a standard solution of a complex-forming agent (producing no coloration) until a sudden change from violet 'red to pink occurs. Complete decelerationof the solution cannot be brought about-by means of.

carbocyclic aromatic nucleus.

2. A derivative of an acid-base indicator dyestuff, which contains the radical of the formula an excess of the'solution, because at the-chosen=pH-value 10 (gm-COOK the barium-free indicatoris" also. lightpink- It is or "OHYN advantage to usefor comparison a solution whichhas- GET-000E.

been titrated out. The residual pink coloration. can also be'compensated for by the addition ofasmall traceof in at least one ortho position to hydroxybgmup of yellow green dyestuff,-for.example,.amixture of .malaa chite green and methyl red. The color-change is especially sharp when only a smallquantity of barium ions is present. I

As the standard solution :there may be used 'a solution of 011 mol' of the disodium salt to ethylene diami'netetracetic acid per liter of'aqueous solution. Somewhat phenolic character, and which.contains.atmost'three monocyclic carbocyclic aromatic nuclei;

the triphenyl-methane-dyestufif series, which contains the radical of the formula 0 0H more sharp 1s the color change when the tetra-alkah salt' CH? O of diamino-diethyl-glycol ether tetracetic acid of the formula I OHCO0H HOOC-CH: /CH2COOH N-CH:CH:OCHrCH:-O-CHzCHzN\ HOOC-CH: CH --COOH is used as the complex-forming agent in the standard in at least one ortho-position to a hydroxy group of solution. phenolic character.

Strontium can be titrated in the same manner as 4. A derivative of an acid-base indicator dyestufi of barium. the phthalein series, which contains the radical of the Example 7 formula DETERMINATION -or= SULFATE CHr-C O'OH The solution of which thecontent of sulfate is to be -CHzN determined is rendered weakly acid, and slightly more CHPGOOH than the equivalent quantity of barium chloride is added at the boiling temperature. As soon asthe precipitate 7 111 at least 036 ortho'posltlon a hydroxyl g p of has become coarsely crystalline, the mixture is.cooled, P11510116 Chflfaflfifand the suspension is charged into a measuring flask to 40 5. The derivativeof phenolphthalein of the formula no 0 c-om on v on no 0 omo on2o 0 on orig-coon- NHqC omN N-HO- CH2N- Hooo-Hio CHg-C 0on out-coon n00 o-orn a determined volume, thoroughly. shaken, and after the precipitate has settled'an'- aliquot portion is withdrawn for titrating the excess ofbarium. The titration isficarried out in the manner described in' Example 6; with the use "of the same indicatorand a standard solution of the same complex=forming agent.

Owing to the fact that the barium complex of the phenolphthalein derivative usedis so stable that theiinon \N H C i on H o dica'tor responds slightly to the concentration of barium z 3 a 6. The derivative. of ortho-cresol phthalein. of; the formula I CHz-CiOOH;

' CH2-N suspended in the form of" barium sulfate, it is necessary Boom-Cg in determiningthe sulfate ions to remove the barium sulfate before the excess of barium ions is back titrated with a complex-forming agent.

What We claim is: 1. A derivative of an acid-base indicator dyestufi, which contains the radical of the formula CHE-000B 7. In the process of determining metal ions by forma- 2 tion of complexes, wherein said complex formation is CHPCOOH made visible by the addition of an indicator which forms 3. A derivative of an acid-base indicator dyestuff of:

ant-coon;

selected from the class consisting of unsubstituted amino I monocyclic carbocyclic aromatic nucleus.

2,745,720 7 7 I N p sa complex with the metal ion to be determined, said comresponsive to complex formation is a derivative of an plex formation producing a change in color, the modification wherein the indicator which is responsive to complex contains the radical of the formula 1 formation ,is a derivative of an acid-base indicator dyeonrooon stufi, WhlCh contains the radical of the formula 5 I CH CH2COOH 2 an N CHa'-C OOH in at least one ortho-position to a hydroxyl group of GHQ-CODE:

phenolic character.

11. In the process of determining alkaline earth metal ions by formation of complexes, wherein said complex formation is made visible by the addition of an indicator which forms a complex with the metal ion to be determined, said complex formation producing a change in 8. In the process of determining metal ions by formacolor, the modification wherein the indicator which is tion of complexes, wherein said complex formation is responsive to complex formation is the derivative of made visible by the addition of an indicator which forms phenolphthalein of the formula in at least one position vicinal to an auxochromic group 10 groups and hydroxyl groups of phenolic character, the amino groups and hydroxyl groups being bound to a no 0 o-orn 0H OH 11000-13120 I CHa-COOE CHTCOOH N-HzC- CHaN N-HzC- CH:N

HQOC-HzC CHz-COOH CH2COOH HOOC-CHa,

a complex with the metal ion to be determined, said 12. In the process of determining alkaline earth metal complex formation producing a change in color, the modiions by formation of complexes, wherein said complex fication wherein the indicator which is responsive to formation is made visible by the addition of an indicator complex formation is a derivative of an acid-base indiwhich forms a complex with the metal ion to be detercator dyestufi', which contains the radical of the formula mined, said complex formation producing a change in color, the modification wherein the indicator which is CH=COOH 40 responsive to complex formation is the derivative of -CH2N V ortho-cresol phthalein of the formula CHPCOOH OH p OH in at least one ortho-position to a hydroxyl group of 30094311 I CHTCOOH phenolic character, and which contains at most three N-HgC- CH; H1O- CHrN monocyclic carbocyclic aromatic nuclei.

9. In the process of determining metal ions by forma- H000 CHI CHTCOOH tion of complexes, wherein said complex formation is made visible by the addition of an indicator which forms a complex with the metal ion to be determined, said V complex formation producing a change in color, the t modification wherein the indicator which is responsive 0 to complex formation is a derivative of an ,acid-base indicator dyestulf of the triphenyl-methane-dye'stuff series, 9 which contains the radical of the formula CHPC O OH References Cited in the file of this patent CHN UNITED STATES PATENTS 2,122,409 Clarke July 5, 1938 ,Q 2,562,198 McKinney July 31, 1951 in at least one ortho-posltion to a hydroxyl group of 2,583,891 Schwarzenbach Jam 29, 1952 1311510110 character- 2,624,756 Bersworth Jan. 6, 1953 10. In the process of determining alkaline earth metal 2,624,757 Bersworth Jan 6, 1953 710118 y fqrmatwn 9i s p r hq 831d 9 3 1 2, 24,753 Bersworth n, 1 5 formation is made visible by the addition of an indicator 2,624,759 Bersworth Jan 6 1953 which forms a complex with the metal 1011 to be deter frnined, said complex formation producing a change in FOREIGN PATENTS color, the modification wherein the indicator which is 48,570 5, 1938 France J an.

acid-base indicator dyestuif of the phthalein series, which i 

1. A DERIVATIVE OF AN ACID-BASE INDICATOR DYESTUFF, WHICH CONTAINS THE RADICAL OF THE FORMULA 